The continuing importance of asymmetric organic synthesis in drug design and discovery has fueled the search for new synthetic methods and chiral precursors. This research effort has resulted in the identification of many new synthetic methods and chiral precursors which have been utilized in developing complex molecules of biological interest.
One important class of chiral molecules are the α-substituted carboxylic acids. These molecules have long been recognized as important chiral precursors to a wide variety of complex biologically active molecules. In particular, a great deal of research effort has been dedicated to the development of methods for the synthesis of enantiomerically pure α-amino acids. Recently, there has been an increasing demand for enantiomerically pure α-amino acids for a variety of uses, including, for example, chiral medicines.
A common synthetic route to α-amino acids is the Strecker synthesis, shown below:
Reversible addition of cyanide and ammonia to the aldehyde or ketone produces an amino nitrile intermediate, which, upon hydrolysis, yields the desired α-amino acid. Although this synthesis has been used to produce racemic amino acids on an industrial scale, there has been only moderate success in developing chiral versions of the Strecker synthesis.
Accordingly, there is a need in the art for efficient, inexpensive, high-yield synthetic methods for producing enantiomerically pure α-substituted carboxylic acids, such as, for example, α-amino acids and α-hydroxy acids.